Abstract
The potential involvement of CYP3A43 in systemic olanzapine (OLA) metabolism has been suggested by one reported association between the intronic polymorphism CYP3A43 rs472660G>A and OLA clearance in 235 White and African-American patients. Trough plasma OLA concentrations in AA carriers were predicted on average 48% lower than in GG carriers. In the current study, we evaluated this finding by genotyping 374 White psychiatric patients on long-term OLA treatment. No significant difference in dose-adjusted trough serum OLA concentrations was observed between the seven AA carriers identified and the other two genotypes, without (P=0.6) or with (P=0.23) adjustment for additional covariates previously known to influence systemic OLA exposure. Because of the low prevalence of the rs472660 AA genotype in White populations (2%), larger study cohorts are needed for future association confirmation. Overall, CYP3A43 rs472660 is not likely to be a major contributor towards variability in systemic OLA exposure among White patients.
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